Inefficient clearance of myelin debris by microglia impairs remyelinating processes

DOI PDF 13 Citations
  • Antoine Lampron
    Department of Molecular Medicine, Faculty of Medicine, Neuroscience Laboratory, CHU de Québec Research Center, Laval University, Quebec City, Quebec 2G1V 4G2, Canada 1
  • Antoine Larochelle
    Department of Molecular Medicine, Faculty of Medicine, Neuroscience Laboratory, CHU de Québec Research Center, Laval University, Quebec City, Quebec 2G1V 4G2, Canada 1
  • Nathalie Laflamme
    Department of Molecular Medicine, Faculty of Medicine, Neuroscience Laboratory, CHU de Québec Research Center, Laval University, Quebec City, Quebec 2G1V 4G2, Canada 1
  • Paul Préfontaine
    Department of Molecular Medicine, Faculty of Medicine, Neuroscience Laboratory, CHU de Québec Research Center, Laval University, Quebec City, Quebec 2G1V 4G2, Canada 1
  • Marie-Michèle Plante
    Department of Molecular Medicine, Faculty of Medicine, Neuroscience Laboratory, CHU de Québec Research Center, Laval University, Quebec City, Quebec 2G1V 4G2, Canada 1
  • Maria Gabriela Sánchez
    Department of Molecular Medicine, Faculty of Medicine, Neuroscience Laboratory, CHU de Québec Research Center, Laval University, Quebec City, Quebec 2G1V 4G2, Canada 1
  • V. Wee Yong
    Department of Clinical Neurosciences and the Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada 2
  • Peter K. Stys
    Department of Clinical Neurosciences and the Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada 2
  • Marie-Ève Tremblay
    Department of Molecular Medicine, Faculty of Medicine, Neuroscience Laboratory, CHU de Québec Research Center, Laval University, Quebec City, Quebec 2G1V 4G2, Canada 1
  • Serge Rivest
    Department of Molecular Medicine, Faculty of Medicine, Neuroscience Laboratory, CHU de Québec Research Center, Laval University, Quebec City, Quebec 2G1V 4G2, Canada 1

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<jats:p>An imbalance between remyelinating and demyelinating rates underlies degenerative processes in demyelinating diseases such as multiple sclerosis. An optimal therapeutic strategy would be to stimulate remyelination while limiting demyelination. Although accumulation of myelin debris impairs remyelination, the mechanisms regulating the clearance of such debris by mononuclear phagocytic cells are poorly understood. We demonstrate that after cuprizone intoxication, CCR2-dependent infiltration of mouse bone marrow–derived cells is abundant in demyelinating areas, but that these cells do not impact demyelination. However, in CX3CR1-deficient mice, the clearance of myelin debris by microglia was blocked greatly, affecting the integrity of the axon and myelin sheaths and thus preventing proper remyelination. These results highlight the crucial role played by CX3CR1 in myelin removal and show that there can be no efficient remyelination after a primary demyelinating insult if myelin clearance by microglia is impaired.</jats:p>

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